Our study represents an evaluation of all TEEs diagnosed in patients with solid tumors within a two-year period at a single institution. The study showed a majority of venous TEEs, with the most common being DVT (50%) and PE (38.5%). Incidental diagnoses and symptomatic diseases were similar (~ 50% each), with a 31% requiring hospitalization. Khorana Scores were intermediate and high (77.4%) in this population. The most common risk factors identified in the study included female sex, elevated BMI, hypertension and diabetes co-morbidities, metastatic stage, colorectal and breast cancer sites, and anti-neoplastic therapy administration within the last two months of presentation.
The study highlights several aspects, some of which are controversial, related to TEEs in cancer patients. One of these is sex. Many reports have suggested that TEEs are more common in females (12, 27); others, however, have not confirmed this finding (28–30). In our study, the majority of our subjects who had TEEs (69.0%) were females. Certain comorbidities (cardiovascular, hypertension, diabetes, and obesity) have been shown to considerably increase the risk for TEE development (31). In our study, 47 (27.0%) and 37 (21.3%) of the patients had hypertension and diabetes, respectively. These numbers are not different from the incidence of diabetes and hypertension in the general population in our region (32, 33).
Colorectal cancer was the commonest cancer seen in our study, with 33 patients representing 19% of our patient’s population. This finding is not consistent with many other studies (5, 13, 34) and might indicate a higher risk for TEEs in our colorectal patients, which represents the second commonest solid tumor after breast cancer, seen at our institution(35). Breast cancer represents a low-risk type of malignancy in most risk models, such as Khorana Score (23, 27); however, it was the second most common malignancy (18.4%) with TEEs in our patient population.
We also looked at other reported risk factors that affect the incidence of TEEs in cancer patients. Performance status is one of them. Previous reports have demonstrated that poor performance status is an important risk factor for VTEs in cancer patients (34, 36). In our study, patients with ECOG performance status scores of 2 or more had the highest frequency (47.7%) of TEEs. However, the percentage of patients with ECOG performance status 1 was still relatively high (30.5%). Advanced stage and anti-neoplastic therapy are other important identified risk factors (13, 37, 38). In our study, 71.8% of patients had metastatic disease, 75% were on anti-neoplastic therapy, and 65.5% had metastatic disease and were on anti-neoplastic therapy. Of note, capecitabine and oxaliplatin were the most common agents used medications in our cohort of patients. An epirubicin, oxaliplatin, and capecitabine (EOX) regimen had been implicated, with an increased incidence of TEEs in gastric and esophageal cancer patients receiving pre-operative or peri-operative chemotherapy (39, 40). Most of the data related to capecitabine and oxaliplatin in colorectal cancer were, however, coupled with bevacizumab, which has thromboembolic properties in itself (41, 42). Twenty-four (13.8%) of the TEEs were catheter-related. Catheter-related thrombosis was low but more common than expected. Historically, catheter-related TEEs are more likely to be diagnosed incidentally and to occur in PICC lines than implantable catheters (43, 44). Hospitalization is also an important risk factor for TEEs in general (45), and more so for cancer-associated TEEs (32). This risk factor did represent one-fourth (23%) of all TEEs diagnosed in our study group.
TEEs in cancer patients adversely affect survival whether discovered symptomatically or incidentally through routine imaging (46, 47). In our study, nearly half of the TEE cases presented with incidental VTE. These findings were supported by other studies showing that incidental VTE accounts for half of TEE cases (48, 49). In addition to affecting survival, TEE in cancer patients places a humanistic and economic burden on patients and institutions (50). In our study, around one-third (31%) of our patients had to be admitted for their TEEs.
Several attempts have been made to identify patients at high risk of developing TEEs by developing risk assessment models. The most used model has been the Khorana scoring system (23). Many other risk assessment models have also been established (27, 29, 32). The majority of the patients in our study fell in the intermediate and high-risk score for the Khorana Model, constituting 77.4%. Recently, two trials tested the efficacy of oral anticoagulants in the prevention of venous thromboembolic events in patients with intermediate or high-risk Khorana Scores. In the CASSINI trial, rivaroxaban significantly reduced the number of VTEs and VTE-related deaths during the on-treatment period (50). Similarly, in the AVERT trial, apixaban resulted in a significantly lower rate of VTE than the placebo in patients with intermediate and high-risk Khorana Scores (51).
Our study has several limitations. First, it is a single institution and a retrospective study. Additionally, the study does not calculate the incidence of TEE in our patients’ population.